Perinatal toxicity of ethylene glycol dimethyl ether in the rat

Ethylene glycol dimethyl ether (EGdiME) was administered by gavage to pregnant Sprague-Dawley rats in doses of 30, 60, 120, 250, 500, and 1000 mg/kg/day from day 8 through day 18 of gestation. The effects of the compound on maternal weight gain, length of gestation, perinatal mortality, teratogenicity, average fetal weight on day 19, and average pup weight one day after birth were assessed. A clear pattern of dose-dependent maternal and fetal toxicity was observed. EGdiME caused maternal deaths at 1000 mg/kg/day and was fetolethal at doses ranging from 120 to 1000 mg/kg/day. A dose of 60 mg/kg/day resulted in a 7% weight decrease and severe edema in pups surviving to birth. Skeletal examinations in this group revealed fetotoxicity as evidenced by the lack of ossified bone, but there was no indication of anomalies in soft tissues. The same concentration in dams allowed to go to term resulted in a delay in the onset of parturition and produced litters with only one-third the number of live pups as controls. Of these, an average of less than 1 per litter survived to day 1 postpartum. The compound was not fetolethal on day 19 at a dose level of 30 mg/kg/day. Perinatal mortality in the interval between day 19 of gestation and birth was manifested, however, by an average reduction of 2 live pups per litter at birth. There was a close correlation between the fetotoxic effects of the various concentrations and the degree to which the maternal weight gain pattern of each departed from the control profile.